EP0282913B2 - Process for the preparation of aromatic sulfones - Google Patents

Process for the preparation of aromatic sulfones Download PDF

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Publication number
EP0282913B2
EP0282913B2 EP88103802A EP88103802A EP0282913B2 EP 0282913 B2 EP0282913 B2 EP 0282913B2 EP 88103802 A EP88103802 A EP 88103802A EP 88103802 A EP88103802 A EP 88103802A EP 0282913 B2 EP0282913 B2 EP 0282913B2
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EP
European Patent Office
Prior art keywords
mixture
cyclic
general formula
terpenoid
acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP88103802A
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German (de)
English (en)
French (fr)
Other versions
EP0282913B1 (en
EP0282913A1 (en
Inventor
Takashi Onishi
Shigeaki Suzuki
Toshiki Mori
Yoshiji Fujita
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kuraray Co Ltd
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Kuraray Co Ltd
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Publication date
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Application filed by Kuraray Co Ltd filed Critical Kuraray Co Ltd
Publication of EP0282913A1 publication Critical patent/EP0282913A1/en
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides

Definitions

  • This invention relates to a process for preparing cyclic terpenoids of general formula (I), wherein R is a hydrogen atom or a lower alkyl group.
  • the cyclic terpenoids of general formula (I) are valuable as intermediates for the synthesis of vitamin A acid and vitamin A acetate which are in use of medicines and feed additives. (See Otera et al., J. Am. Chem. Soc., 106, 3670 (1984) ; Otera et al., J. Org. Chem., 51, 3834 (1986))
  • the conventional methods of preparing cyclic terpenoids are cyclization reaction of acyclic terpenoids under acidic conditions.
  • the cyclic terpenoids necessary for the synthesis of vitamin A acid and vitamin A acetate are the compounds of general formula (I) (hereinafter referred to as ⁇ -form).
  • the terpenoids prepared by a conventional method contain ⁇ -form and also cyclic terpenoids of general formula (II) (hereinafter referred to as a-form) as a by-product. wherein R is the same as defined above. Consequently the yield of ⁇ -form at the cyclization becomes low, and a complicated process for the separation of by-product a-form such as silica gel chromatography and the like are needed.
  • an object of the invention is to provide a process for preparing ⁇ -form. the starting material of vitamin A acid and vitamin A acetate, at a good yield in a commercial scale.
  • the present invention provides a process for preparing a mixture of cyclic terpenoids of general formula (I), wherein R is hydrogen atom or a lower alkyl group, and general formula (II), wherein R is the same as defined above, containing the cyclic terpenoid of general formula (I) predominant over (II) by the reaction of an acid and a cyclic terpenoid of of general formula (II) or a mixture of cyclic terpenoids of general formulas (II) and (I), containing the cyclic terpenoid of general formula (II) predominant over (I).
  • a cyclic terpenoid of general formula (I) can be separated by crystallization from a mixture of cyclic terpenoids of general formulas (I) and (II), containing the cyclic terpenoid of general formula (I) predominant cover (II).
  • This mixture of cydic terpenoids of general formulas (I) and (II), containing the cyclic terpenoid of general formula (I) predominant over (II) can be prepared by the action of an acid with an acydic terpenoid of general formula (III), wherein R is a hydrogen atom or a lower alkyl group, and a mixture of cyclic terpenoids of general formulas (I) and (II).
  • R is a hydrogen atom or a lower alkyl group, such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl and the like, which can be substituted at any position of ortho-(o-), meta-(m-), and para-(p-) to sulfonyl-group.
  • more particularly preferable substitutions are hydrogen atom and p-methyl group.
  • the process of this invention including the separation of pform by crystallization basically consists of the following two steps.
  • the mixture of a-form and ⁇ -form in which a-form is predominant over ⁇ -form recovered from the mother liquor of operation 2) can be converted to a mixture of a-form and ⁇ -form in which ⁇ -form is predominant over a-form.
  • ⁇ -form can be efficiently obtained by recycling these operations.
  • the mixture of a-form and ⁇ -form in which ⁇ -form is predominant over a-form can be prepared by the reaction of an acid and a-form, a mixture of a-form and ⁇ -form in which a-form is predominant over ⁇ -form, or a mixture of an acyclic terpenoid of general formula (III) and this mixture.
  • the acids used are sulfuric acid ; a mixture of sulfuric acid and lower aliphatic carboxylic acids, such as formic acid, acetic acid and the like ;; and a mixture of sulfuric acid and water.
  • a preferable amount of acid is in the range of from 0.5 to 20 times, more preferably from 0.3 to 5 times per mole of a-form, the sum of a-form and ⁇ -form, or the sum of a-fomm, (3-form and an acyclic terpenoid of general formula (III).
  • a preferable reaction temperature depending on the type and amount of acid is usually in the range of from -10°C to 150°C, and a preferable reaction time is in the range of from 1 minute to 10 hours.
  • the Solvent used is a hydrocarbon, such as butane, pentane, hexane, heptane, benzene, toluene and xylene.
  • a preferable amount of solvent to acid is practically in the range of from 0.1 to 50 times, more particularly from 0.5 to 30 times by volume.
  • the ratio of a-form to ⁇ -form, ⁇ -form/ ⁇ -form can be 1040/90-60 after the reaction with an acid.
  • ⁇ -form can be separated by crystallization after the increasing of the ratio of ⁇ -form.
  • Preferable solvents for crystallization are aliphatic hydrocarbons, such as hexane, heptane and the like; aromatic hydrocarbons, such as benzene, toluene, xylene and the like; aliphatic ethers, such as ethyl ether, propyl ether and the like; aliphatic alcohols, such as methanol, ethanol, propanol and the like ; aliphatic ketones, such as acetone, methyl ethyl ketone and the like ; aliphatic esters of carboxylic acids, such as methyl acetate, ethyl acetate and the like; as a single or mixed solvent.
  • a crystallizing temperature depending on the type of solvent is usually in the range of from the reflux temperature to -50°C.
  • An amount of solvent is used in the range of from 0.1 to 200 times by volume to the sum of a-form and ⁇ -form.
  • the mother liquor separated from ⁇ -form, distilled off the solvent when used under normal pressure or reduced pressure provides a mixture of a-form and ⁇ -form in which a-form is predominant over ⁇ -form.
  • the obtained mixture, mixed with a-form, or further mixed with an acyclic terpenoid of general formula (III) can be transmitted to a mixture of a-form and ⁇ -form in which ⁇ -form is predominant over a-form by the reaction of an acid, and can be used for the separation of pform by crystallization.
  • the recycling of these operations provides practically ⁇ -form only efficiently in commercial scale production.
  • the mother liquor can be used untouched or after the removal of high boiling part by molecular distillation and the like.
  • viscous oil was dissolved in 300 ml of a mixed solution of hexane and benzene (volume ratio of hexane/benzene was 9713) at reflux, and gradually cooled and then kept for 5 hours at 10°C.
  • the deposited crystal was filtered with a glass filter to give 30.9 g of white crystal.
  • the obtained crystal was found to ba a mixture of [2] and [3], the ratio of [2]/[3] being 5.0/95.0.
  • the solvent in mother liquor after crystallization was subjected to distillation under reduced pressure to give 33.7 g (purity 83.7%, net 28.8 g) of viscous oil.
  • the obtained product was found a mixture of [2] and [3], the ratio of [2]/[3] being 55.3/44.7 by gas chromatography.
  • the obtained mixture was dissolved in 150 ml of a mixed solution of haxane and benzene (volume ratio of hexane/benzene was 97/3) at reflux, and the same procedure was repeated as described above, and 14.1 g of crystal was obtained.
  • the crystal was found to be a mixture of [2] and [3], the ratio of [2]/[3] being 4.2/95.8.
  • the solvent in mother liquor after crystallization was removed by distillation under reduced pressure to give 15.4 g of brown viscous oil (purity 85.7%, net 13.2 g).
  • the obtained product was found a mixture of [2] and [3], the ratio of [2]/[3] being 51.8/48.2 by gas chromatography.
  • the obtained brown viscous oil (21.2 g) was dissolved in 200 mol of hexane at reflux, and gradually cooled and kept for 20 hours at room temperature.
  • the deposited white crystal was filtered with a glass filter, and 11.5 g of crystal was obtained.
  • the obtained crystal was a mixture of [5] and [6], the ratio of [5]/[6] being 5/95.
  • the solvent in the mother liquor after crystallization was removed by distillation under reduced pressure to give 7.2 g (purity 85%, net 6.1 g of brown viscous oil.
  • the ratio of [5] and [6], [5]/[6] being 56.9/43.1 was found by gas chromatography.
  • Example 2 The same procedure of Example 1 was repeated except that a mixture (the ratio of [2] and [3], [2]/[3] 65.13/34.87, purity 68.48%) was used in sulfuric acid-acetic acid system, wherein the volume of acetic acid was the same of that of concentrated sulfuric acid, and the volume of pentane was 5 times of that of acetic acid.
  • a mixture the ratio of [2] and [3], [2]/[3] 65.13/34.87, purity 68.48%) was used in sulfuric acid-acetic acid system, wherein the volume of acetic acid was the same of that of concentrated sulfuric acid, and the volume of pentane was 5 times of that of acetic acid.
  • the results are shown as in the following table.
  • the results are shown as in the following table.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
EP88103802A 1987-03-17 1988-03-10 Process for the preparation of aromatic sulfones Expired - Lifetime EP0282913B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP62063417A JPH0822846B2 (ja) 1987-03-17 1987-03-17 環状テルペン化合物の製造方法
JP63417/87 1987-03-17

Publications (3)

Publication Number Publication Date
EP0282913A1 EP0282913A1 (en) 1988-09-21
EP0282913B1 EP0282913B1 (en) 1991-06-19
EP0282913B2 true EP0282913B2 (en) 1993-10-20

Family

ID=13228693

Family Applications (1)

Application Number Title Priority Date Filing Date
EP88103802A Expired - Lifetime EP0282913B2 (en) 1987-03-17 1988-03-10 Process for the preparation of aromatic sulfones

Country Status (6)

Country Link
US (1) US4924030A (ja)
EP (1) EP0282913B2 (ja)
JP (1) JPH0822846B2 (ja)
DE (1) DE3863302D1 (ja)
DK (1) DK175137B1 (ja)
FI (1) FI90066C (ja)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013081642A1 (en) * 2011-12-01 2013-06-06 Bikam Pharmaceuticals, Inc. Opsin-binding ligands, compositions and methods of use

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2515437A1 (de) * 1974-04-16 1975-11-20 Ici Ltd Verfahren zur kristallisation von bis(4-chlorphenyl)sulfon
JPS5188938A (en) * 1975-01-31 1976-08-04 Kojundo 4*4** jikurorujifuenirusurupponnobunrihoho
JPS51133252A (en) * 1975-05-15 1976-11-18 Kuraray Co Ltd Process for preparing cyclic terpene derivatives
JPS6042788B2 (ja) * 1978-03-06 1985-09-25 株式会社クラレ 新規な置換シクロヘキセン誘導体およびその製法
JPS5748549A (en) * 1980-08-29 1982-03-19 Fujitsu Ltd Testing method for paper sheet multifeed checking apparatus
FR2565974B1 (fr) * 1984-06-19 1986-08-22 Rhone Poulenc Sante Nouveau procede de p

Also Published As

Publication number Publication date
JPS63227563A (ja) 1988-09-21
DK142988A (da) 1988-09-18
DK175137B1 (da) 2004-06-14
DE3863302D1 (de) 1991-07-25
FI881253A0 (fi) 1988-03-16
FI881253A (fi) 1988-09-18
EP0282913B1 (en) 1991-06-19
FI90066C (fi) 1993-12-27
US4924030A (en) 1990-05-08
EP0282913A1 (en) 1988-09-21
JPH0822846B2 (ja) 1996-03-06
DK142988D0 (da) 1988-03-16
FI90066B (fi) 1993-09-15

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